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WO2002059098A1 - Derives de thiazole et d'oxazole en tant qu'activateurs de recepteurs actives par le proliferateur du peroxysome humain - Google Patents

Derives de thiazole et d'oxazole en tant qu'activateurs de recepteurs actives par le proliferateur du peroxysome humain Download PDF

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Publication number
WO2002059098A1
WO2002059098A1 PCT/US2001/051056 US0151056W WO02059098A1 WO 2002059098 A1 WO2002059098 A1 WO 2002059098A1 US 0151056 W US0151056 W US 0151056W WO 02059098 A1 WO02059098 A1 WO 02059098A1
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
phenyl
trifluoromethyl
thiazol
sulfanyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2001/051056
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English (en)
Inventor
Pierette Banker
Rodolfo Cadilla
Millard Hurst Lambert, Iii
Stephen William Rafferty
Daniel David Sternbach
Marcos Luis Sznaidman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Glaxo Group Ltd
Original Assignee
Glaxo Group Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd
Priority to DK01994514T priority Critical patent/DK1349843T3/da
Priority to AT01994514T priority patent/ATE293611T1/de
Priority to DE60110262T priority patent/DE60110262T2/de
Priority to JP2002559400A priority patent/JP4234431B2/ja
Priority to EP01994514A priority patent/EP1349843B1/fr
Publication of WO2002059098A1 publication Critical patent/WO2002059098A1/fr
Anticipated expiration legal-status Critical
Priority to US11/550,060 priority patent/US7229998B2/en
Priority to US11/753,848 priority patent/US7449468B2/en
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/24—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/26—Radicals substituted by sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/28—Radicals substituted by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to certain novel compounds.
  • the present invention relates to compounds that activate human peroxisome proliferator activated receptors ("hPPARs").
  • hPPARs human peroxisome proliferator activated receptors
  • the present invention also relates to methods for preparing the compounds, their use in medicine, pharmaceutical compositions containing them and methods for the prevention or treatment of PPAR mediated diseases or conditions.
  • Syndrome X (including metabolic syndrome) is loosely defined as a collection of abnormalities including hyperinsulinemia, obesity, elevated levels of trigycerides, uric acid, fibrinogen, small dense LDL particles, and plasminogen activator inhibitor 1 (PAI-1), and decreased levels of HDL-c.
  • abnormalities including hyperinsulinemia, obesity, elevated levels of trigycerides, uric acid, fibrinogen, small dense LDL particles, and plasminogen activator inhibitor 1 (PAI-1), and decreased levels of HDL-c.
  • NIDDM is described as insulin resistance which in turn causes anomalous glucose output and a decrea ⁇ e in glucose uptake by skeletal muscle. These factors eventually leaci to impaired glucose tolerance (IGT) and hyperinsulinemia.
  • Peroxisome Proliferator Activated Receptors PPARs are ophan receptors belonging to the steroid/retinoid receptor superfamily of ligand-activated transcription factors. See, for example Willson T.M. and Wahli, W., Curr. Opin. Chem. Biol. (1997) Vol 1 pp 235-241 and Willson T.M. et. al., J. Med. Chem (2000) Vol 43 p527-549.
  • R 1 and R 2 are independently hydrogen or C,. 3 alkyl
  • X 2 is O, S, or CH 2 ;
  • R 3 , R 4 , and R 5 are independently H, C ⁇ alkyl, OCH 3 , CF 3 , OCF 3 , allyl, CN, or halogen;
  • Y is S or O; each R 25 is independently CH 3 , OCH 3 , OCF 3 , CF 3 , or halogen; y is O, 1 , 2, 3, 4 or 5; and
  • the formulations may include other agents conventional in the art having regard to the type of formulation in question, for example those suitable for oral administration may include flavouring agents.
  • reference herein to treatment extends to prophylaxis as well as the treatment of established diseases or symptoms.
  • the amount of a compound of the invention required for use in treatment will vary with the nature of the condition being treated and the age and the condition of the patient and will be ultimately at the discretion of the attendant physician or veterinarian. In general, however, doses employed for adult human treatment will typically be in the range of 0.02-5000 mg per day, preferably 1-1500 mg per day.
  • the desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals, for example as two, three, four or more sub-doses per day.
  • the formulations according to the invention may contain between 0.1-99% of the active ingredient, conveniently from 30-95% for tablets and capsules and 3-50% for liquid preparations.
  • Ethyl 4-(hydroxymethyl)-2-[4-(trifluoromethyl)phenyl]-1 ,3-thiazole-5-carboxylate 42g, 0.127moles, 1eq
  • dry CH 2 Cl 2 300ml
  • reaction mixture was then washed with 0.1 N HCI and the phases were separated, with discarding the aqueous fraction.
  • the organic fraction was washed with 0.1 N HCI, H 2 0, brine and dried over Na 2 S0 4 .
  • the solution was filtered and concentrated in vacuo to yield 119.95g (98%) of pure sulfonyl chloride.
  • Ethyl 2- ⁇ 4-[( ⁇ 4-(2-thienylmethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl ⁇ methyl)sulfanyl]-2- methylphenoxy ⁇ propanoate From 5-(chloromethyl)-4-(3-furylmethyl)-2-[4-(trifluoromethyl)phenyl]-1 ,3-thiazole (0.185g, 0.50 mmol), ethyl 2- ⁇ 4-[( ⁇ 4-(2-thienylmethyl)-2-[4-(trifluoromethyl)phenyl]-1 ,3-thiazol-5- yl ⁇ methyl)sulfanyl]-2-methyIphenoxy ⁇ propanoate (0.21 g, 73%) was obtained as a yellow solid.
  • reaction mixture was cooled to -78°C followed by the dropwise addition of neat ⁇ [tert- Butyl(diphenyl)silyl]oxy ⁇ acetyl chloride (18g, 54mmoles, 1eq) over a period of 15 minutes maintaining the internal reaction temperature below -60°C.
  • Phenylboronic acid (0.143g, 1.2mmoles, 1.5eq) was then added followed by the addition of sodium carbonate (2M aqueous solution, 2.3ml, 4.68mmoles, 6eq).
  • the reaction mixture was heated at 100 degrees centigrade for 13 hours at which point, after cooling to room temperature, the reaction was partitioned between EtOAc and water. After separation of the phases the organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, concentrated in vacuo to yield after purification by silica gel chromatography (CH 2 CI 2 to 2% MeOH/CH 2 Cl 2 ) 268mg (80%) of product.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Emergency Medicine (AREA)
  • Neurology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Child & Adolescent Psychology (AREA)
  • Biomedical Technology (AREA)
  • Endocrinology (AREA)
  • Neurosurgery (AREA)
  • Nutrition Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un composé représenté par la formule (I) : (I) dans laquelle R1-R5, R25, R26, Y et X2 répondent à leur définition de la revendication 1. Ces composés activent les récepteurs activés par le proliférateur du peroxysome humain (hPPARs) et sont utiles pour le traitement de maladies associées, telles que la maladie cardio-vasculaire et l'hypercholestérolémie.
PCT/US2001/051056 2000-12-20 2001-12-19 Derives de thiazole et d'oxazole en tant qu'activateurs de recepteurs actives par le proliferateur du peroxysome humain Ceased WO2002059098A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
DK01994514T DK1349843T3 (da) 2000-12-20 2001-12-19 Thiazol- og oxazolderivater som aktivatorer af human peroxisom profilerator-aktiverede receptorer
AT01994514T ATE293611T1 (de) 2000-12-20 2001-12-19 Thiazol und oxazol-derivate als aktivatoren von menschlichen peroxisom proliferator aktivierten rezeptoren
DE60110262T DE60110262T2 (de) 2000-12-20 2001-12-19 Thiazol und oxazol-derivate als aktivatoren von menschlichen peroxisom proliferator aktivierten rezeptoren
JP2002559400A JP4234431B2 (ja) 2000-12-20 2001-12-19 ヒトペルオキシソーム増殖因子活性化受容体の活性化剤としてのチアゾール及びオキサゾール誘導体
EP01994514A EP1349843B1 (fr) 2000-12-20 2001-12-19 Derives de thiazole et d'oxazole en tant qu'activateurs de recepteurs actives par le proliferateur du peroxysome humain
US11/550,060 US7229998B2 (en) 2000-12-20 2006-10-17 Thiazole and oxazole derivatives as activators of human peroxisome proliferator activated receptors
US11/753,848 US7449468B2 (en) 2000-12-20 2007-05-25 Thiazole and oxazole derivatives as activators of human peroxisome proliferator activated receptors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0031103.5 2000-12-20
GBGB0031103.5A GB0031103D0 (en) 2000-12-20 2000-12-20 Chemical compounds

Related Child Applications (2)

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US10451295 A-371-Of-International 2001-12-19
US11/550,060 Continuation US7229998B2 (en) 2000-12-20 2006-10-17 Thiazole and oxazole derivatives as activators of human peroxisome proliferator activated receptors

Publications (1)

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WO2002059098A1 true WO2002059098A1 (fr) 2002-08-01

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PCT/US2001/051056 Ceased WO2002059098A1 (fr) 2000-12-20 2001-12-19 Derives de thiazole et d'oxazole en tant qu'activateurs de recepteurs actives par le proliferateur du peroxysome humain

Country Status (9)

Country Link
EP (1) EP1349843B1 (fr)
JP (1) JP4234431B2 (fr)
AT (1) ATE293611T1 (fr)
DE (1) DE60110262T2 (fr)
DK (1) DK1349843T3 (fr)
ES (1) ES2240558T3 (fr)
GB (1) GB0031103D0 (fr)
PT (1) PT1349843E (fr)
WO (1) WO2002059098A1 (fr)

Cited By (35)

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WO2003015776A1 (fr) * 2001-08-13 2003-02-27 Janssen Pharmaceutica N.V. Derives de thiazolyl 2,4,5-trisubstitue et activite anti-inflammatoire associee
WO2003072102A1 (fr) 2002-02-25 2003-09-04 Eli Lilly And Company Modulateurs des récepteurs activés par les proliférateurs de peroxisomes
WO2004022551A1 (fr) * 2002-09-06 2004-03-18 Takeda Pharmaceutical Company Limited Derive de furane ou de thiophene, et ses utilisations pharmaceutiques
WO2004026849A1 (fr) * 2002-09-19 2004-04-01 Smithkline Beecham Corporation Procede de preparation d'acides phenoxyacetiques a partir de phenols
WO2004037775A1 (fr) 2002-10-28 2004-05-06 Novo Nordisk A/S Nouveaux composes traitant les maladies mediees par le ppar
WO2004037776A2 (fr) 2002-10-28 2004-05-06 Novo Nordisk A/S Nouveaux composes, leur preparation et leur utilisation
WO2004076428A1 (fr) * 2003-02-27 2004-09-10 Aventis Pharma Deutschland Gmbh Derives d'acide 4-(3-(2-phenyl-oxazol-4-ylmethoxy)-cyclohexyloxy)-butanoique et composes apparentes en tant que modulateurs de ppar dans le traitement du diabete de type 2 et de l'atherosclerose
WO2004000785A3 (fr) * 2002-06-19 2004-10-14 Smithkline Beecham Corp Composes chimiques
JP2005035966A (ja) * 2002-09-06 2005-02-10 Takeda Chem Ind Ltd フランまたはチオフェン誘導体およびその医薬用途
US7091245B2 (en) 2002-09-05 2006-08-15 Novo Novdisk A/S Compounds, their preparation and use
US7105551B2 (en) 2000-12-20 2006-09-12 Smithkline Beecham Corporation Thiazole derivatives for treating PPAR related disorders
US7129268B2 (en) 2002-10-28 2006-10-31 Novo Nordisk A/S Peroxisome proliferator activated receptor-active arylene acetic acid derivatives
WO2007003581A1 (fr) 2005-06-30 2007-01-11 Novo Nordisk A/S Acides phénoxyacétiques en tant qu'activateurs de rapp-delta
US7196107B2 (en) 2000-12-20 2007-03-27 Smithkline Beecham Corporation Thia-and oxazoles and their use as ppars activators
US7223761B2 (en) 2003-10-03 2007-05-29 Amgen Inc. Salts and polymorphs of a potent antidiabetic compound
FR2910893A1 (fr) * 2006-12-29 2008-07-04 Genfit Sa Derives de (phenylthiazolyl)-phenyl-propan-1-one et de (phenyloxazolyl)-phenyl-propan-1-one substitues, preparations et utilisations.
US7601841B2 (en) 2000-06-28 2009-10-13 Amgen Inc. Quinolinyl and benzothiazolyl modulators
US7626033B2 (en) 1999-06-30 2009-12-01 Amgen Inc. Compounds for the modulation of PPARγ activity
US7709528B2 (en) 2002-10-28 2010-05-04 High Point Pharmaceuticals, Llc Compounds, their preparation and use
EP2213289A1 (fr) 2006-09-07 2010-08-04 Nycomed GmbH Combinaison pour le Traitement de mellitus de diabète
US7943612B2 (en) 2006-03-09 2011-05-17 High Point Pharmaceuticals, Llc Compounds that modulate PPAR activity, their preparation and use
US7943613B2 (en) 2005-12-22 2011-05-17 High Point Pharmaceuticals, Llc Compounds, their preparation and use
US7968723B2 (en) 2004-05-05 2011-06-28 High Point Pharmaceuticals, Llc Compounds, their preparation and use
US8053598B2 (en) 2004-05-05 2011-11-08 High Point Pharmaceuticals, Llc Compounds, their preparation and use
WO2012122368A1 (fr) * 2011-03-08 2012-09-13 The Regents Of The University Of California Composés de liaison à la désoxycytidine kinase
US8404726B2 (en) 2006-04-18 2013-03-26 Nippon Chemiphar Co. Ltd. Activating agent for peroxisome proliferator activated receptor δ
US8648208B2 (en) 2008-04-15 2014-02-11 Nippon Chemiphar Co. Ltd. Activating agent for peroxisome proliferator activated receptor
WO2015068156A1 (fr) 2013-11-05 2015-05-14 Ben-Gurion University Of The Negev Research And Development Authority Composés pour le traitement du diabète et des complications pathologiques qui en résultent
US9579335B2 (en) 2010-10-19 2017-02-28 Indiana University Research And Technology Corporation Treatment of cystic diseases
US9663448B2 (en) 2007-06-04 2017-05-30 Ben-Gurion University Of The Negev Research And Development Authority Tri-aryl compounds and compositions comprising the same
US10456406B2 (en) 2013-09-09 2019-10-29 Vtv Therapeutics Llc Use of a PPAR-δ agonist for reducing loss of muscle strength, muscle mass, or type I muscle fibers in an immobilized limb
US11446307B2 (en) 2020-11-02 2022-09-20 Trethera Corporation Crystalline forms of a deoxycytidine kinase inhibitor and uses thereof
WO2022245986A1 (fr) * 2021-05-19 2022-11-24 Stinginn Inc Petits inhibiteurs moléculaires de compositions de signalisation sting et méthodes d'utilisation
US11931365B2 (en) 2022-01-25 2024-03-19 Reneo Pharmaceuticals, Inc. Use of PPAR-delta agonists in the treatment of disease
US12134605B2 (en) 2019-12-18 2024-11-05 Stinginn, Llc Substituted 1,2,4-triazoles and methods of use

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BRPI0610177A2 (pt) * 2005-05-25 2016-11-29 Nippon Chemiphar Co composto ou um sal do mesmo, e, ativador para receptor ativado por proliferador de peroxissomo
JP2009132620A (ja) * 2006-03-07 2009-06-18 Astellas Pharma Inc フェニルチアゾール誘導体

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WO2000008002A1 (fr) * 1998-08-07 2000-02-17 Glaxo Group Limited OXAZOLES SUBSTITUES ET DERIVES DE THIAZOLES COMME ACTIVATEURS DE ALPHA hPPAR ET DE GAMMA hPPAR
WO2001000603A1 (fr) * 1999-06-25 2001-01-04 Glaxo Group Limited Derives de thiazol et d'oxazole et utilisation pharmaceutique de ceux-ci
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EP1349843B1 (fr) 2005-04-20
DK1349843T3 (da) 2005-08-15
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